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MCC > Wk 6 Metastasis > Flashcards

Wk 6 Metastasis Flashcards

1
Q

What are the 5 steps of metastasis?

A
  1. local invasion
  2. intravasation
  3. circulation
  4. extravasation
  5. colonization
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2
Q

What % of human cancers are carcinomas?

A

80%

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3
Q

Normal fxns of epithelia?

A
  1. protection/barrier function
  2. secretion
  3. absorption
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4
Q

What happens to epithelial cells during tumor formation?

A

MMPs get secreted from tumor cells and modify ECM, breaking through the ECM, allowing the cancer cells to migrate
-invasion = have gone through the matrix

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5
Q

How is a cell’s polarity determined?

A

By the attachment of integrins to the ECM - determines basal side w/ apical side at other end

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6
Q

How is a cell’s polarity determined?

A

By the attachment of integrins to the ECM - determines basal side w/ apical side at other end

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7
Q

What is E-cadherin

A

protein in adherens junctions that hold cells together

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8
Q

What tissues are made of epithelial cells?

A

skin/organ lining/ducts

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9
Q

What tissues are made of epithelial cells?

A

skin/organ lining/ducts

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10
Q

What cells do cancer cells follow into circ?

A

intravasation behind macrophages

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11
Q

What is extravasation?

A

Getting out of the BV

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12
Q

What does ECM cause epithelial cells to do?

A

self-organize as polarized duct-like acini
-need ECM to survive so ones in middle will die w/o ECM contact, creating a duct

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13
Q

What 2 signals does the ECM send to epithelial cells?

A
  1. survival
  2. polarization
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14
Q

How is carcinogenesis different than normal epithelium?

A

tumor epithelial cells can survive w/o ECM contact

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15
Q

Summary of norm epithelium vs tumor epithelium

A
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16
Q

What is a common feature of progression in many tumors?

A

Loss of E-cadherin, which fascilitates cell-cell detachment

17
Q

What is trapped in ECM that regulate cell proliferation, survival, polarity and migration?

A

growth factors

18
Q

How do cancer cells move?

A

move along ECM fibers that are aligned by cancer-associated fibroblasts
-actin pulls on/along ECM proteins

19
Q

What are the protein heterodimers that bind cells to ECM?

A

Integrins
intracellularly, bind to signaling proteins and cytoskeleton
extracellularly, bind to ECM
-allow for communication b/w ECM and cell

20
Q

Summary of cell attachement and migration

A
21
Q

What do we feel most often if feel a lump (think breast lump)

A

The ECM surrounding cancer cells

22
Q

More integrin allows what?

A

More movement

23
Q

Is cell migration sufficient for metastasis?

A

No, b/c still need to invade

23
Q

What breaks down the ECM?

A

proteases: MMPs and others

24
Q

Where are MMPs normally made?

A

Made and secreted by stromal cells (macrophages, activated fibroblasts)
-are not normally secreted by epithelial cells, but many tumor cells can overexpress MMPs OR induce stromal/immune cells to make them

25
Q

How do ECM fibers look near tumors?

A

more linear -> rigidity and makes for a migratory highway
ECM stiffness also contributes to growth - integrins and GF receptor cross-talk

26
Q

Key point

A

cancer cells remodel the matrix and use it to move throughout the body

27
Q

End summary

A
28
Q

What is EMT?

A

Epithelial cells “remember” how to migrate and invade from an essential developmental process called the epithelial- mesenchymal transition (EMT)

29
Q

Besides cancer, when does EMT occur?

A

Gastrulation at the primitive streak

30
Q

What are 6 similarities b/w developmental and cancer metastasis EMT subtypes?

A
31
Q

What are 3 differences b/w developmental EMT and cancer metastasis?

A
32
Q

How is cancer metastasis like wound healing?

A

inflammation
BV remodeling
MMPs

33
Q

How does EMT assist metastasis?

A
34
Q

How do tumor vessels look compared to normal vessels?

A

large, unorganized and leaky

35
Q

What do tumors produce a lot of?

A

VEGF protein

36
Q

How does the tumor microenvironment contribute to metastasis?

A

MCC (44 decks)

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